Refractive errors, which include nearsightedness (myopia) and farsightedness (hyperopia) are the most common causes of preventable visual impairment worldwide. The prevalence of myopia in the United States and globally has increased significantly within the last 3 decades. By 2020, one third of the world?s population?over 2.5 billion people?will be affected by myopia alone. Refractive errors are a significant Public Health problem in the US where over 40% of people are nearsighted by adulthood. This proportion is expected to rise, as it has in East Asia where myopia afflicts up to 90% of young adults in urban areas. Refractive error development is influenced by complex networks of environmental, behavioral, and genetic factors from early childhood. Within the last five years, we and others have discovered over three dozen genetic loci that influence refractive errors, myopia development, and related traits. These genes, however, explain only about 5% of the variation of refractive errors in the population. This represents a small fraction of refractive error heritability estimates, which typically range from 60 to >90%. Epidemiological studies have convincingly shown that environmental and behavioral factors influence the risk of developing myopia. For example, greater exposure to near work and higher educational attainment are significant and consistent risk factors for myopia. Our primary objective is to build a comprehensive genetic model of refractive development in humans by analyzing data from the UK Biobank (UKBB), the largest single resource of genetic epidemiological data on refractive error. We will conduct large-scale whole-genome association studies in up to 440,000 UKBB participants for which data on refractive error and myopia age-at-onset are available. These analyses will give us unprecedented power to replicate and discover new refractive error loci that will explain the ?missing heritability? of refractive phenotypes. We will also take advantage of the unprecedented sample size to discover rare genetic variants that cause severe, potentially blinding, refractive disorders. The results will allow us to better understand the complex etiology of refractive errors, and provide a solid foundation for the future development of myopia prediction, prevention, and treatment strategies. Ultimately, a more complete understanding of genetic and environmental causes of myopia will inform medical and public health scientists about preventative measures to help stem the tide of the global ?myopia epidemic?.